The primary purpose of the proposed study is the relationship between folic acid and vitamin B12. The specific objectives are: 1) To study the effect of methionine on the absorption of folic acid by vitamin B12-deficient livers with a view to determine whether the mechanism resides in the effect on transport into the cell or the effect of methionine in influencing the synthesis of polyglutamates inside the cell. 2) To study the synthesis of folic acid polyglutamates in liver. Polyglutamate synthetase in liver will be purified and the role of various folic acid substrates determined. 3) To study the mechanism whereby thyroxine modifies folic acid and vitamin B12 metabolism. Thyroxine has been found to increase vitamin B12 requirement and impair folic acid metabolism in both humans and animals. The effect of thyroidectomy and thyroxine on various vitamin B12-and folic acid-dependent enzymes will be studied.